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Radiother Oncol. 2019 Nov 8;144:13-22. doi: 10.1016/j.radonc.2019.10.011. [Epub ahead of print]

Prognostic importance of radiologic extranodal extension in HPV-positive oropharyngeal carcinoma and its potential role in refining TNM-8 cN-classification.

Author information

1
Department of Radiation Oncology, the Princess Margaret Cancer Centre/University of Toronto, Canada; Department of Otolaryngology - Head & Neck Surgery, the Princess Margaret Cancer Centre/University of Toronto, Canada. Electronic address: shaohui.huang@rmp.uhn.on.ca.
2
Department of Radiation Oncology, the Princess Margaret Cancer Centre/University of Toronto, Canada; Department of Otolaryngology - Head & Neck Surgery, the Princess Margaret Cancer Centre/University of Toronto, Canada.
3
Department of Biostatistics, the Princess Margaret Cancer Centre/University of Toronto, Canada.
4
Department of Neuroradiology and Head and Neck Imaging, Princess Margaret Cancer Centre/University of Toronto, Canada.
5
Department of Radiation Oncology, the Princess Margaret Cancer Centre/University of Toronto, Canada.
6
Department of Otolaryngology - Head & Neck Surgery, the Princess Margaret Cancer Centre/University of Toronto, Canada.
7
Division of Medical Oncology, the Princess Margaret Cancer Centre/University of Toronto, Canada.

Abstract

PURPOSE:

This study examines outcome heterogeneity and potential to refine the TNM-8 cN-classification using radiologic extranodal extension (rENE) in a contemporary HPV-positive (HPV+) oropharyngeal carcinoma (OPC) cohort.

METHODS:

All HPV+ OPC treated with definitive IMRT from 2010-2015 were included. Pre-treatment CT/MR of cN+ cases were reviewed by a head-neck radiologist for rENE. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) vs rENE-negative (rENE-). Multivariable analysis (MVA) for OS confirmed the prognostic value of rENE. Refined cN-classifications for new TNM staging proposals were evaluated against TNM-8 using established criteria.

RESULTS:

A total of 517 cN+ (rENE+: 97; rENE-: 420) and 41 cN0 cases were identified. The rENE+ proportion increased with rising N-category (N1/N2/N3: 11%/19%/84%, p < 0.001). Median follow-up was 5.1 years. Compared to rENE-, rENE+ patients had a lower 5-year OS (56% vs 85%) and DFS (46% vs 83%) overall, and in N1 (OS: 57% vs 89%; DFS: 51% vs 87%) and N2 subsets (OS: 45% and 76%; DFS: 33% vs 74%) (all p < 0.001). MVA confirmed the prognostic value of rENE for OS (HR = 3.86, p < 0.001) and DFS (HR = 3.89, p < 0.001). We proposed two new cN-classifications: Schema1 reclassified any N_rENE+ as New_N3; Schema2 reclassified N1_rENE+ as New_N2 and N2_rENE+ as New_N3. Stage incorporating either Schema1 (ranked 1st) or Schema2 (ranked 2nd) cN-categories outperformed TNM-8.

CONCLUSION:

This study confirms that rENE is prognostically important and facilitates understanding of known outcome heterogeneity within TNM-8 in HPV+ OPC patients. rENE is a promising parameter to refine the TNM-8 cN-classifications.

KEYWORDS:

HPV; Oropharyngeal carcinoma; Outcome; Prognosis; Staging; cN-classification

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